ArticleJournal of gastroenterology2026
TP53 mutation predicts resistance to immune checkpoint inhibitor-based therapy in intrahepatic cholangiocarcinoma.
Article in Journal of gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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Who cites it
4 citing papers in PubMed.
- Review
- The Evolving Landscape of Immune Regulation and Immunotherapy in Cholangiocarcinoma and Biliary Tract Cancer.Cancers · 2026Review
- Comprehensive Genomic Profiles of Patients With Biliary Tract Cancer.Cancer medicine · 2026Article
- Tertiary lymphoid structure topotypes in intrahepatic cholangiocarcinoma: spatial immunity, checkpoint-response associations, and therapeutic reprogramming.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
backgroundIntrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with limited treatment options and a poor prognosis. Although immune checkpoint inhibitor (ICI)-based chemotherapy has recently been introduced as a first-line treatment, clinical responses remain highly variable. Currently, no reliable molecular biomarkers are available to predict the therapeutic efficacy of ICC.
methodsWe conducted a retrospective, multicenter cohort study of 25 patients with unresectable ICC treated with gemcitabine, cisplatin, and durvalumab (GCD therapy) between September 2022 and August 2024. Comprehensive genomic profiling was performed in 19 patients (76%) to identify genomic alterations. In selected cases, spatial transcriptomic analysis using the Xenium platform was employed to characterize tumor-immune spatial dynamics.
resultsThe median progression-free survival (PFS) was 7.8 months (95% CI: 3.6-10.6), and the median overall survival (OS) was 11.1 months (95% CI: 6.9-18.6). Among genomic alterations, TP53 mutation was the only independent predictor of shorter PFS in multivariate analysis (HR: 4.20; p = 0.036). TP53-mutant tumors were associated with significantly shorter PFS (p = 0.011) and a trend toward worse OS (p = 0.051). Spatial transcriptomic profiling revealed a distinct immunosuppressive microenvironment in TP53-mutated tumors marked by poor CD8⁺ T-cell infiltration, enrichment of CD109⁺ tumor-associated macrophages, and downregulation of antigen-presentation genes TAP1 and TAP2.
conclusionsThis study is the first to identify TP53 mutation as a biomarker of resistance to ICI-based therapy in ICC, and to uncover its immune-evasive phenotype using spatial profiling. These findings provide mechanistic insight into immune evasion and support the development of TP53-guided immunotherapeutic strategies in ICC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.